1. Field of the Invention
The present invention relates to novel, transient prodrug derivatives of the biologically active compounds which contain a mercapto moiety, and, more especially, relates to certain acyl-X-methylthioether latentiated forms of such thio compounds.
As employed in this application, the expression "prodrug" denotes a derivative of a known and proven prior art compound, which derivative, when absorbed into the bloodstream of a warm-blooded animal, "cleaves" in such a manner as to release the proven drug form and permits the same to attain a higher bioavailability level than that which could be obtained if the proven drug form, per se, was administered.
Furthermore, also as used in this application, the term "transient" denotes "cleavage" of the compounds of this invention in such a manner that the proven drug form is released and the remaining "cleaved" moiety is non-toxic and metabolized in such a manner that non-toxic, metabolic products are produced.
2. Description of the Prior Art
It is well known to this art that the biologically active compounds which contain a mercapto group (--SH) and their salts, e.g., cysteine, cysteine methyl ester, N-acetylcysteine, penicillamine, dimercaprol, thiopental, 2-mercaptopyridine N-oxide, methimazole, propylthiouracil, N-(2-methyl-3-thio-propionyl)proline, 2-thiouracil, 6-mercaptopurine, glutathione, 6-thioguanine, 6-thioguanosine, 6-mercaptopurineriboside, as well as corresponding protected ester derivatives and salts are useful active agents for the treatment or management of a wide variety of disease states or conditions, e.g., cancer, psoriasis, hypertension, fungal infections, hyperthyroidism, metal poisoning, excess mucus, pain (general anesthesia).
Nevertheless, it too is well known to the art that such mercapto containing compounds, and the various art-recognized therapeutically active derivatives thereof, are characterized by certain inherent disadvantages, notably serious bioavailability and physiological availability problems upon administration. Such reduced availability can be attributed in part to poor lipid solubility [by reason of the presence of the hydrophilic mercapto group], and also to metabolic losses during and following conventional administration. Other disadvantages associated with the prior art compounds are instability to both air and light, and same are subject to chemical attack by many agents that are conventionally used in pharmaceutical preparations, as well as a variety of other unfavorable pharmacodynamic properties.
Thus, there exists a clear and present need for novel latentiated forms of biologically active substances containing mercapto moieties which derivatives would be devoid of those disadvantages and drawbacks that to date have characterized the prior art compounds.